Epithelia, regardless of location, function as protective barriers which are often specialized to actively transport electrolytes or nutrients. Derangements of those functions result in disease. The stratified squamous epithelium of the mammalian esophagus acts as a barrier against gastric acid, and also actively transports sodium from the lumen to the blood. These properties dictate the broad goals of the proposed research: (1) To investigate the role of active and passive electrolyte transport by this epithelium in the pathophysiology of esophagitis and (2) to determine if an easily measured hallmark of that transport function--the transmural, electrical potential difference (P.D.)--is useful in detecting or quantifying diseases of the esophageal mucosa in man (e.g., esophagitis, Barrett's esophagus, and esophageal carcinoma). The pathophysiology of esophagitis will be investigated in animals. The effect of acute and chronic hydrochloric acid administration on active electrolyte transport, and on the magnitude and permselectivity of the paracellular shunt path (tight junctional-intracellular space complex), will be correlated with the structure of the epithelium particularly its junctional complexes. The role of synergistic agents such as bile salts, alcohol, and aspirin will also be explored. The major investigational techniques will be in vitro, using chamber-type studies of transport combined with electron microscopy. The esophageal P. D. will be measured in man simultaneously with pressure by a technique devised for use with routine esophageal manometric testing. The P. D. values and patterns obtained will be correlated with clinical history and course, other existing tests of esophageal function, and with histology. These studies at the cellular level offer new insights into the pathophysiology of esophagitis by studies of the mucosa rather than the esophageal muscle; promise possible new clinical techniques for the diagnosis and/or prognosis of esophageal mucosal diseases; and define the interrelationship between the transport and barrier function of epithelia.